HRP20000373A2 - Hydroxamic acid derivatives as matrix metalloprotease (mmp) inhibitors - Google Patents

Info

Publication number

HRP20000373A2

HRP20000373A2 HR20000373A HRP20000373A HRP20000373A2 HR P20000373 A2 HRP20000373 A2 HR P20000373A2 HR 20000373 A HR20000373 A HR 20000373A HR P20000373 A HRP20000373 A HR P20000373A HR P20000373 A2 HRP20000373 A2 HR P20000373A2

Authority

HR

Croatia

Prior art keywords

preparation

title compound

brs

ylsulfonyl

mmol

Prior art date

1997-12-05

Links

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• 239000002253 acid Substances 0.000 title claims description 16
• 239000003112 inhibitor Substances 0.000 title claims description 15
• 102000005741 Metalloproteases Human genes 0.000 title description 5
• 108010006035 Metalloproteases Proteins 0.000 title description 5
• NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 title description 4
• 239000011159 matrix material Substances 0.000 title description 3
• 150000001875 compounds Chemical class 0.000 claims description 390
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 210
• 238000000034 method Methods 0.000 claims description 191
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 169
• 239000000203 mixture Substances 0.000 claims description 147
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 70
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 57
• -1 2,3-dihydrobenzofuranyl Chemical group 0.000 claims description 44
• 150000003839 salts Chemical class 0.000 claims description 44
• 239000001257 hydrogen Substances 0.000 claims description 36
• 229910052739 hydrogen Inorganic materials 0.000 claims description 36
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 35
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 33
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 32
• 239000002904 solvent Substances 0.000 claims description 31
• 238000006243 chemical reaction Methods 0.000 claims description 27
• 150000002431 hydrogen Chemical class 0.000 claims description 26
• 239000012453 solvate Substances 0.000 claims description 26
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 24
• 239000002585 base Substances 0.000 claims description 19
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 claims description 18
• VKUYLANQOAKALN-UHFFFAOYSA-N 2-[benzyl-(4-methoxyphenyl)sulfonylamino]-n-hydroxy-4-methylpentanamide Chemical group C1=CC(OC)=CC=C1S(=O)(=O)N(C(CC(C)C)C(=O)NO)CC1=CC=CC=C1 VKUYLANQOAKALN-UHFFFAOYSA-N 0.000 claims description 15
• 102100030416 Stromelysin-1 Human genes 0.000 claims description 15
• 101710108790 Stromelysin-1 Proteins 0.000 claims description 15
• 239000003814 drug Substances 0.000 claims description 15
• 150000002148 esters Chemical class 0.000 claims description 12
• 125000005843 halogen group Chemical group 0.000 claims description 12
• 208000010125 myocardial infarction Diseases 0.000 claims description 12
• 201000010099 disease Diseases 0.000 claims description 11
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
• 238000004519 manufacturing process Methods 0.000 claims description 11
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
• 206010028980 Neoplasm Diseases 0.000 claims description 10
• 125000000217 alkyl group Chemical group 0.000 claims description 10
• 239000006184 cosolvent Substances 0.000 claims description 10
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical group CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 9
• 201000011510 cancer Diseases 0.000 claims description 9
• 229910052799 carbon Inorganic materials 0.000 claims description 9
• 229940079593 drug Drugs 0.000 claims description 9
• 238000009472 formulation Methods 0.000 claims description 9
• 201000008482 osteoarthritis Diseases 0.000 claims description 9
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 9
• 238000011282 treatment Methods 0.000 claims description 9
• 208000037260 Atherosclerotic Plaque Diseases 0.000 claims description 8
• 229940124761 MMP inhibitor Drugs 0.000 claims description 8
• 241000124008 Mammalia Species 0.000 claims description 8
• 206010027476 Metastases Diseases 0.000 claims description 8
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 8
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
• 230000005747 tumor angiogenesis Effects 0.000 claims description 8
• 208000025865 Ulcer Diseases 0.000 claims description 7
• 206010064930 age-related macular degeneration Diseases 0.000 claims description 7
• 230000003683 cardiac damage Effects 0.000 claims description 7
• 230000003176 fibrotic effect Effects 0.000 claims description 7
• 210000004969 inflammatory cell Anatomy 0.000 claims description 7
• 208000027866 inflammatory disease Diseases 0.000 claims description 7
• 208000002780 macular degeneration Diseases 0.000 claims description 7
• 230000001617 migratory effect Effects 0.000 claims description 7
• 208000017520 skin disease Diseases 0.000 claims description 7
• 125000001424 substituent group Chemical group 0.000 claims description 7
• 230000036269 ulceration Effects 0.000 claims description 7
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 6
• 241001465754 Metazoa Species 0.000 claims description 6
• 125000003545 alkoxy group Chemical group 0.000 claims description 6
• 125000005605 benzo group Chemical group 0.000 claims description 6
• 125000004432 carbon atom Chemical group C* 0.000 claims description 6
• 239000003795 chemical substances by application Substances 0.000 claims description 6
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
• 239000000825 pharmaceutical preparation Substances 0.000 claims description 6
• 230000029663 wound healing Effects 0.000 claims description 6
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 5
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
• 125000001153 fluoro group Chemical group F* 0.000 claims description 5
• 150000003512 tertiary amines Chemical class 0.000 claims description 5
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 5
• 125000004414 alkyl thio group Chemical group 0.000 claims description 4
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
• 239000003085 diluting agent Substances 0.000 claims description 4
• 208000028169 periodontal disease Diseases 0.000 claims description 4
• AEGNSAJEPASCEB-UHFFFAOYSA-N 2-[4-[4-(3-ethoxyphenyl)-3-methoxyphenyl]piperidin-1-yl]sulfonyl-n-hydroxy-2-methylpropanamide Chemical compound CCOC1=CC=CC(C=2C(=CC(=CC=2)C2CCN(CC2)S(=O)(=O)C(C)(C)C(=O)NO)OC)=C1 AEGNSAJEPASCEB-UHFFFAOYSA-N 0.000 claims description 3
• DMYSRZBLJSUUJP-UHFFFAOYSA-N 2-[4-[4-(3-ethoxyphenyl)-3-methylphenyl]piperidin-1-yl]sulfonyl-n-hydroxy-2-methylpropanamide Chemical compound CCOC1=CC=CC(C=2C(=CC(=CC=2)C2CCN(CC2)S(=O)(=O)C(C)(C)C(=O)NO)C)=C1 DMYSRZBLJSUUJP-UHFFFAOYSA-N 0.000 claims description 3
• JQFYDWDOFHGYLD-UHFFFAOYSA-N 2-[4-[4-(6-ethoxypyridin-2-yl)-3-methylphenyl]piperidin-1-yl]sulfonyl-n-hydroxy-2-methylpropanamide Chemical compound CCOC1=CC=CC(C=2C(=CC(=CC=2)C2CCN(CC2)S(=O)(=O)C(C)(C)C(=O)NO)C)=N1 JQFYDWDOFHGYLD-UHFFFAOYSA-N 0.000 claims description 3
• BWOKVQMLEBMZFQ-UHFFFAOYSA-N 2-[[4-[4-(3-ethoxyphenyl)-3-methylphenyl]-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]-n-hydroxy-2-methylpropanamide Chemical compound CCOC1=CC=CC(C=2C(=CC(=CC=2)C=2CCN(CC=2)S(=O)(=O)C(C)(C)C(=O)NO)C)=C1 BWOKVQMLEBMZFQ-UHFFFAOYSA-N 0.000 claims description 3
• JYHCJUBSWRQINP-UHFFFAOYSA-N 2-[[4-[4-(3-ethoxyphenyl)-3-methylphenyl]-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]-n-hydroxyacetamide Chemical compound CCOC1=CC=CC(C=2C(=CC(=CC=2)C=2CCN(CC=2)S(=O)(=O)CC(=O)NO)C)=C1 JYHCJUBSWRQINP-UHFFFAOYSA-N 0.000 claims description 3
• 239000007821 HATU Substances 0.000 claims description 3
• 230000003213 activating effect Effects 0.000 claims description 3
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 3
• 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 claims description 3
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
• 125000002541 furyl group Chemical group 0.000 claims description 3
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 3
• 125000001041 indolyl group Chemical group 0.000 claims description 3
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 3
• 125000002950 monocyclic group Chemical group 0.000 claims description 3
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
• JRIUEEGXFJPYTG-UHFFFAOYSA-N n-hydroxy-2-[4-[4-[3-(2-methoxyethoxy)phenyl]-3-methylphenyl]piperidin-1-yl]sulfonyl-2-methylpropanamide Chemical compound COCCOC1=CC=CC(C=2C(=CC(=CC=2)C2CCN(CC2)S(=O)(=O)C(C)(C)C(=O)NO)C)=C1 JRIUEEGXFJPYTG-UHFFFAOYSA-N 0.000 claims description 3
• 125000001624 naphthyl group Chemical group 0.000 claims description 3
• 125000004076 pyridyl group Chemical group 0.000 claims description 3
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 3
• 125000001544 thienyl group Chemical group 0.000 claims description 3
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 2
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
• 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 2
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 claims description 2
• 229910052783 alkali metal Inorganic materials 0.000 claims description 2
• 230000015572 biosynthetic process Effects 0.000 claims description 2
• 229910052740 iodine Inorganic materials 0.000 claims description 2
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
• 125000005394 methallyl group Chemical group 0.000 claims description 2
• KQOMFRMJZJNRQB-UHFFFAOYSA-N n-hydroxy-1-[4-[4-(3-methoxyphenyl)-3-methylphenyl]piperidin-1-yl]sulfonylcyclobutane-1-carboxamide Chemical compound COC1=CC=CC(C=2C(=CC(=CC=2)C2CCN(CC2)S(=O)(=O)C2(CCC2)C(=O)NO)C)=C1 KQOMFRMJZJNRQB-UHFFFAOYSA-N 0.000 claims description 2
• QMYFMVWTULBAHS-UHFFFAOYSA-N n-hydroxy-1-[4-[4-(3-methoxyphenyl)-3-methylphenyl]piperidin-1-yl]sulfonylcyclopentane-1-carboxamide Chemical compound COC1=CC=CC(C=2C(=CC(=CC=2)C2CCN(CC2)S(=O)(=O)C2(CCCC2)C(=O)NO)C)=C1 QMYFMVWTULBAHS-UHFFFAOYSA-N 0.000 claims description 2
• 230000002265 prevention Effects 0.000 claims description 2
• 230000008569 process Effects 0.000 claims description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 5
• 238000009109 curative therapy Methods 0.000 claims 4
• 238000011321 prophylaxis Methods 0.000 claims 4
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 2
• 150000001340 alkali metals Chemical class 0.000 claims 1
• 125000005587 carbonate group Chemical group 0.000 claims 1
• 238000002360 preparation method Methods 0.000 description 519
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 204
• 239000007787 solid Substances 0.000 description 188
• 239000000243 solution Substances 0.000 description 121
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 114
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 96
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 92
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 76
• 239000000126 substance Substances 0.000 description 74
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 72
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 72
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 69
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 57
• 235000019341 magnesium sulphate Nutrition 0.000 description 57
• 239000011541 reaction mixture Substances 0.000 description 48
• 239000012074 organic phase Substances 0.000 description 42
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 40
• 229910052757 nitrogen Inorganic materials 0.000 description 36
• 238000004587 chromatography analysis Methods 0.000 description 35
• OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 35
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 32
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 30
• 239000003480 eluent Substances 0.000 description 30
• 238000010992 reflux Methods 0.000 description 30
• ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 28
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 28
• 239000003921 oil Substances 0.000 description 23
• 235000019198 oils Nutrition 0.000 description 23
• 238000010828 elution Methods 0.000 description 22
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 21
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
• YBIPZPBGAGTBGK-UHFFFAOYSA-N methyl 2-chlorosulfonylacetate Chemical compound COC(=O)CS(Cl)(=O)=O YBIPZPBGAGTBGK-UHFFFAOYSA-N 0.000 description 21
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 20
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 20
• 239000012230 colorless oil Substances 0.000 description 20
• 239000000758 substrate Substances 0.000 description 20
• 102000004190 Enzymes Human genes 0.000 description 19
• 108090000790 Enzymes Proteins 0.000 description 19
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 19
• 238000002425 crystallisation Methods 0.000 description 19
• 230000008025 crystallization Effects 0.000 description 19
• 238000003818 flash chromatography Methods 0.000 description 18
• ROUYFJUVMYHXFJ-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)CC1 ROUYFJUVMYHXFJ-UHFFFAOYSA-N 0.000 description 18
• 239000000284 extract Substances 0.000 description 17
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
• 229910000104 sodium hydride Inorganic materials 0.000 description 15
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical group [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 14
• 229910000027 potassium carbonate Inorganic materials 0.000 description 14
• 239000012312 sodium hydride Substances 0.000 description 14
• 239000012258 stirred mixture Substances 0.000 description 14
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 13
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 13
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• 102100026802 72 kDa type IV collagenase Human genes 0.000 description 9
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• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
• 229960000583 acetic acid Drugs 0.000 description 8
• XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical group [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 8
• 239000003054 catalyst Substances 0.000 description 8
• 239000000706 filtrate Substances 0.000 description 8
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• 239000011734 sodium Substances 0.000 description 8
• 238000012360 testing method Methods 0.000 description 8
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 8
• WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 8
• COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical group CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 8
• 238000003776 cleavage reaction Methods 0.000 description 7
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 7
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• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical group [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 7
• 230000007017 scission Effects 0.000 description 7
• GUEHESDOJBMSSE-UHFFFAOYSA-M (2-aminophenyl)mercury(1+);acetate Chemical compound CC(=O)O[Hg]C1=CC=CC=C1N GUEHESDOJBMSSE-UHFFFAOYSA-M 0.000 description 6
• 102100027995 Collagenase 3 Human genes 0.000 description 6
• 108050005238 Collagenase 3 Proteins 0.000 description 6
• 102000000380 Matrix Metalloproteinase 1 Human genes 0.000 description 6
• 108010016113 Matrix Metalloproteinase 1 Proteins 0.000 description 6
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
• OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 6
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• PSIJIFBJQIGRJB-UHFFFAOYSA-N methyl 2-[4-[4-(3-ethoxyphenyl)-3-methylphenyl]piperidin-1-yl]sulfonyl-2-methylpropanoate Chemical compound CCOC1=CC=CC(C=2C(=CC(=CC=2)C2CCN(CC2)S(=O)(=O)C(C)(C)C(=O)OC)C)=C1 PSIJIFBJQIGRJB-UHFFFAOYSA-N 0.000 description 1
• OUNGSSGQZWVYKT-UHFFFAOYSA-N methyl 2-[4-[4-(3-ethoxyphenyl)-3-methylphenyl]piperidin-1-yl]sulfonylacetate Chemical compound CCOC1=CC=CC(C=2C(=CC(=CC=2)C2CCN(CC2)S(=O)(=O)CC(=O)OC)C)=C1 OUNGSSGQZWVYKT-UHFFFAOYSA-N 0.000 description 1
• UPTAJYKPVUESOU-UHFFFAOYSA-N methyl 2-[4-[4-(3-methoxyphenyl)-3-methylphenyl]piperidin-1-yl]sulfonyl-1,3-dihydroindene-2-carboxylate Chemical compound C1C2=CC=CC=C2CC1(C(=O)OC)S(=O)(=O)N(CC1)CCC1C(C=C1C)=CC=C1C1=CC=CC(OC)=C1 UPTAJYKPVUESOU-UHFFFAOYSA-N 0.000 description 1
• BCIBBBAQVFPOJN-UHFFFAOYSA-N methyl 2-[4-[4-(3-methoxyphenyl)-3-methylphenyl]piperidin-1-yl]sulfonylacetate Chemical compound C1CN(S(=O)(=O)CC(=O)OC)CCC1C1=CC=C(C=2C=C(OC)C=CC=2)C(C)=C1 BCIBBBAQVFPOJN-UHFFFAOYSA-N 0.000 description 1
• PKKVHEUTNROMJA-UHFFFAOYSA-N methyl 2-[4-[4-(5-ethoxypyridin-3-yl)-3-methylphenyl]piperidin-1-yl]sulfonyl-2-methylpropanoate Chemical compound CCOC1=CN=CC(C=2C(=CC(=CC=2)C2CCN(CC2)S(=O)(=O)C(C)(C)C(=O)OC)C)=C1 PKKVHEUTNROMJA-UHFFFAOYSA-N 0.000 description 1
• KOJLVHCJQBAHBK-UHFFFAOYSA-N methyl 2-[4-[4-(6-ethoxypyridin-2-yl)-3-methylphenyl]piperidin-1-yl]sulfonyl-2-methylpropanoate Chemical compound CCOC1=CC=CC(C=2C(=CC(=CC=2)C2CCN(CC2)S(=O)(=O)C(C)(C)C(=O)OC)C)=N1 KOJLVHCJQBAHBK-UHFFFAOYSA-N 0.000 description 1
• UXAXQQPWSGYVFY-UHFFFAOYSA-N methyl 2-[4-[4-[3-(2-methoxyethoxy)phenyl]-3-methylphenyl]piperidin-1-yl]sulfonyl-2-methylpropanoate Chemical compound COCCOC1=CC=CC(C=2C(=CC(=CC=2)C2CCN(CC2)S(=O)(=O)C(C)(C)C(=O)OC)C)=C1 UXAXQQPWSGYVFY-UHFFFAOYSA-N 0.000 description 1
• OXKFWRCQJKVREC-UHFFFAOYSA-N methyl 2-[[4-(3-fluoro-4-phenylphenyl)-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]acetate Chemical compound C1N(S(=O)(=O)CC(=O)OC)CCC(C=2C=C(F)C(=CC=2)C=2C=CC=CC=2)=C1 OXKFWRCQJKVREC-UHFFFAOYSA-N 0.000 description 1
• MLDZULJDQKJPBE-UHFFFAOYSA-N methyl 2-[[4-(3-methyl-4-phenylphenyl)-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]acetate Chemical compound C1N(S(=O)(=O)CC(=O)OC)CCC(C=2C=C(C)C(=CC=2)C=2C=CC=CC=2)=C1 MLDZULJDQKJPBE-UHFFFAOYSA-N 0.000 description 1
• IXWRCTWJKLSMKK-UHFFFAOYSA-N methyl 2-[[4-(3-methyl-4-pyridin-3-ylphenyl)-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]acetate Chemical compound C1N(S(=O)(=O)CC(=O)OC)CCC(C=2C=C(C)C(=CC=2)C=2C=NC=CC=2)=C1 IXWRCTWJKLSMKK-UHFFFAOYSA-N 0.000 description 1
• UJQMIFFCPGLVKG-UHFFFAOYSA-N methyl 2-[[4-(3-methyl-4-pyridin-4-ylphenyl)-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]acetate Chemical compound C1N(S(=O)(=O)CC(=O)OC)CCC(C=2C=C(C)C(=CC=2)C=2C=CN=CC=2)=C1 UJQMIFFCPGLVKG-UHFFFAOYSA-N 0.000 description 1
• ULNZBDBDSDHGGR-UHFFFAOYSA-N methyl 2-[[4-(4-bromo-3-methylphenyl)-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]-2-methylpropanoate Chemical compound C1N(S(=O)(=O)C(C)(C)C(=O)OC)CCC(C=2C=C(C)C(Br)=CC=2)=C1 ULNZBDBDSDHGGR-UHFFFAOYSA-N 0.000 description 1
• YJYIHELVVMSDFL-UHFFFAOYSA-N methyl 2-[[4-(4-bromo-3-methylphenyl)-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]acetate Chemical compound C1N(S(=O)(=O)CC(=O)OC)CCC(C=2C=C(C)C(Br)=CC=2)=C1 YJYIHELVVMSDFL-UHFFFAOYSA-N 0.000 description 1
• NHLFDJMJJDUEMN-UHFFFAOYSA-N methyl 2-[[4-(4-phenylphenyl)-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]acetate Chemical compound C1N(S(=O)(=O)CC(=O)OC)CCC(C=2C=CC(=CC=2)C=2C=CC=CC=2)=C1 NHLFDJMJJDUEMN-UHFFFAOYSA-N 0.000 description 1
• FCMWTFDDBRVYEJ-UHFFFAOYSA-N methyl 2-[[4-[3-methoxy-4-(3-methoxyphenyl)phenyl]-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]-2-methylpropanoate Chemical compound C1N(S(=O)(=O)C(C)(C)C(=O)OC)CCC(C=2C=C(OC)C(=CC=2)C=2C=C(OC)C=CC=2)=C1 FCMWTFDDBRVYEJ-UHFFFAOYSA-N 0.000 description 1
• XZGIMYUEGPDLAR-UHFFFAOYSA-N methyl 2-[[4-[3-methoxy-4-(3-methoxyphenyl)phenyl]-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]acetate Chemical compound C1N(S(=O)(=O)CC(=O)OC)CCC(C=2C=C(OC)C(=CC=2)C=2C=C(OC)C=CC=2)=C1 XZGIMYUEGPDLAR-UHFFFAOYSA-N 0.000 description 1
• NVVUDBPAARZWAY-UHFFFAOYSA-N methyl 2-[[4-[3-methyl-4-[3-(trifluoromethoxy)phenyl]phenyl]-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]acetate Chemical compound C1N(S(=O)(=O)CC(=O)OC)CCC(C=2C=C(C)C(=CC=2)C=2C=C(OC(F)(F)F)C=CC=2)=C1 NVVUDBPAARZWAY-UHFFFAOYSA-N 0.000 description 1
• NJLYMCJOCCXEPS-UHFFFAOYSA-N methyl 2-[[4-[3-methyl-4-[3-(trifluoromethyl)phenyl]phenyl]-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]acetate Chemical compound C1N(S(=O)(=O)CC(=O)OC)CCC(C=2C=C(C)C(=CC=2)C=2C=C(C=CC=2)C(F)(F)F)=C1 NJLYMCJOCCXEPS-UHFFFAOYSA-N 0.000 description 1
• UOAVCEVHKRGTJK-UHFFFAOYSA-N methyl 2-[[4-[4-(1,2-dimethylbenzimidazol-5-yl)-3-methylphenyl]-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]-2-methylpropanoate Chemical compound C1N(S(=O)(=O)C(C)(C)C(=O)OC)CCC(C=2C=C(C)C(=CC=2)C=2C=C3N=C(C)N(C)C3=CC=2)=C1 UOAVCEVHKRGTJK-UHFFFAOYSA-N 0.000 description 1
• GNBAHEIHRAVMBF-UHFFFAOYSA-N methyl 2-[[4-[4-(1,3-benzodioxol-5-yl)-3-methylphenyl]-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]acetate Chemical compound C1N(S(=O)(=O)CC(=O)OC)CCC(C=2C=C(C)C(=CC=2)C=2C=C3OCOC3=CC=2)=C1 GNBAHEIHRAVMBF-UHFFFAOYSA-N 0.000 description 1
• QWVSYTXGCRRERG-UHFFFAOYSA-N methyl 2-[[4-[4-(2,2-dimethyl-1,3-benzodioxol-5-yl)-3-methylphenyl]-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]-2-methylpropanoate Chemical compound C1N(S(=O)(=O)C(C)(C)C(=O)OC)CCC(C=2C=C(C)C(=CC=2)C=2C=C3OC(C)(C)OC3=CC=2)=C1 QWVSYTXGCRRERG-UHFFFAOYSA-N 0.000 description 1
• PZTHQQMVPJBLEK-UHFFFAOYSA-N methyl 2-[[4-[4-(2,3-dihydro-1-benzofuran-5-yl)-3-methylphenyl]-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]acetate Chemical compound C1N(S(=O)(=O)CC(=O)OC)CCC(C=2C=C(C)C(=CC=2)C=2C=C3CCOC3=CC=2)=C1 PZTHQQMVPJBLEK-UHFFFAOYSA-N 0.000 description 1
• XRZPYBSTSAQVJD-UHFFFAOYSA-N methyl 2-[[4-[4-(2,3-dihydro-1h-inden-5-yl)-3-methylphenyl]-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]acetate Chemical compound C1N(S(=O)(=O)CC(=O)OC)CCC(C=2C=C(C)C(=CC=2)C=2C=C3CCCC3=CC=2)=C1 XRZPYBSTSAQVJD-UHFFFAOYSA-N 0.000 description 1
• WWFDJOVXEIGOIJ-UHFFFAOYSA-N methyl 2-[[4-[4-(2-fluorophenyl)-3-methylphenyl]-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]acetate Chemical compound C1N(S(=O)(=O)CC(=O)OC)CCC(C=2C=C(C)C(=CC=2)C=2C(=CC=CC=2)F)=C1 WWFDJOVXEIGOIJ-UHFFFAOYSA-N 0.000 description 1
• JIWPIEGHPVCNGM-UHFFFAOYSA-N methyl 2-[[4-[4-(3,4-dimethoxyphenyl)-3-methylphenyl]-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]acetate Chemical compound C1N(S(=O)(=O)CC(=O)OC)CCC(C=2C=C(C)C(=CC=2)C=2C=C(OC)C(OC)=CC=2)=C1 JIWPIEGHPVCNGM-UHFFFAOYSA-N 0.000 description 1
• SBNIGSRNMLWKKN-UHFFFAOYSA-N methyl 2-[[4-[4-(3-chloro-4-fluorophenyl)-3-methylphenyl]-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]acetate Chemical compound C1N(S(=O)(=O)CC(=O)OC)CCC(C=2C=C(C)C(=CC=2)C=2C=C(Cl)C(F)=CC=2)=C1 SBNIGSRNMLWKKN-UHFFFAOYSA-N 0.000 description 1
• GZFRWCNASIFMSZ-UHFFFAOYSA-N methyl 2-[[4-[4-(3-ethoxyphenyl)-3-methoxyphenyl]-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]-2-methylpropanoate Chemical compound CCOC1=CC=CC(C=2C(=CC(=CC=2)C=2CCN(CC=2)S(=O)(=O)C(C)(C)C(=O)OC)OC)=C1 GZFRWCNASIFMSZ-UHFFFAOYSA-N 0.000 description 1
• AUYQDUDXYSVNDT-UHFFFAOYSA-N methyl 2-[[4-[4-(3-ethoxyphenyl)-3-methoxyphenyl]-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]acetate Chemical compound CCOC1=CC=CC(C=2C(=CC(=CC=2)C=2CCN(CC=2)S(=O)(=O)CC(=O)OC)OC)=C1 AUYQDUDXYSVNDT-UHFFFAOYSA-N 0.000 description 1
• KJVPAGUHLZZYHV-UHFFFAOYSA-N methyl 2-[[4-[4-(3-ethoxyphenyl)-3-methylphenyl]-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]acetate Chemical compound CCOC1=CC=CC(C=2C(=CC(=CC=2)C=2CCN(CC=2)S(=O)(=O)CC(=O)OC)C)=C1 KJVPAGUHLZZYHV-UHFFFAOYSA-N 0.000 description 1
• YCURSHRSGJXMFB-UHFFFAOYSA-N methyl 2-[[4-[4-(3-ethoxyphenyl)phenyl]-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]acetate Chemical compound CCOC1=CC=CC(C=2C=CC(=CC=2)C=2CCN(CC=2)S(=O)(=O)CC(=O)OC)=C1 YCURSHRSGJXMFB-UHFFFAOYSA-N 0.000 description 1
• DNUPZSDNCDILNY-UHFFFAOYSA-N methyl 2-[[4-[4-(3-ethylphenyl)-3-methylphenyl]-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]acetate Chemical compound CCC1=CC=CC(C=2C(=CC(=CC=2)C=2CCN(CC=2)S(=O)(=O)CC(=O)OC)C)=C1 DNUPZSDNCDILNY-UHFFFAOYSA-N 0.000 description 1
• UUPGXJPULVBCJM-UHFFFAOYSA-N methyl 2-[[4-[4-(3-formylphenyl)-3-methylphenyl]-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]acetate Chemical compound C1N(S(=O)(=O)CC(=O)OC)CCC(C=2C=C(C)C(=CC=2)C=2C=C(C=O)C=CC=2)=C1 UUPGXJPULVBCJM-UHFFFAOYSA-N 0.000 description 1
• FIAJBKSKENNETG-UHFFFAOYSA-N methyl 2-[[4-[4-(3-methoxyphenyl)-3-methylphenyl]-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]acetate Chemical compound C1N(S(=O)(=O)CC(=O)OC)CCC(C=2C=C(C)C(=CC=2)C=2C=C(OC)C=CC=2)=C1 FIAJBKSKENNETG-UHFFFAOYSA-N 0.000 description 1
• KAYSTOBLMMSJIW-UHFFFAOYSA-N methyl 2-[[4-[4-(5-ethoxypyridin-3-yl)-3-methylphenyl]-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]-2-methylpropanoate Chemical compound CCOC1=CN=CC(C=2C(=CC(=CC=2)C=2CCN(CC=2)S(=O)(=O)C(C)(C)C(=O)OC)C)=C1 KAYSTOBLMMSJIW-UHFFFAOYSA-N 0.000 description 1
• WPCPVHRMYNUKOB-UHFFFAOYSA-N methyl 2-[[4-[4-(6-ethoxypyridin-2-yl)-3-methylphenyl]-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]-2-methylpropanoate Chemical compound CCOC1=CC=CC(C=2C(=CC(=CC=2)C=2CCN(CC=2)S(=O)(=O)C(C)(C)C(=O)OC)C)=N1 WPCPVHRMYNUKOB-UHFFFAOYSA-N 0.000 description 1
• SDXLBFLEBCMMSO-UHFFFAOYSA-N methyl 2-[[4-[4-[3-(2-methoxyethoxy)phenyl]-3-methylphenyl]-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]-2-methylpropanoate Chemical compound COCCOC1=CC=CC(C=2C(=CC(=CC=2)C=2CCN(CC=2)S(=O)(=O)C(C)(C)C(=O)OC)C)=C1 SDXLBFLEBCMMSO-UHFFFAOYSA-N 0.000 description 1
• KVUPLHYJILUZBM-UHFFFAOYSA-N methyl 2-[[4-[4-[3-(hydroxymethyl)phenyl]-3-methylphenyl]-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]acetate Chemical compound C1N(S(=O)(=O)CC(=O)OC)CCC(C=2C=C(C)C(=CC=2)C=2C=C(CO)C=CC=2)=C1 KVUPLHYJILUZBM-UHFFFAOYSA-N 0.000 description 1
• IBCBRQIGZHDKSP-UHFFFAOYSA-N methyl 2-[[4-[4-[3-(methoxymethyl)phenyl]-3-methylphenyl]-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]acetate Chemical compound COCC1=CC=CC(C=2C(=CC(=CC=2)C=2CCN(CC=2)S(=O)(=O)CC(=O)OC)C)=C1 IBCBRQIGZHDKSP-UHFFFAOYSA-N 0.000 description 1
• CXMWZLRRELTEGW-UHFFFAOYSA-N methyl 2-[[4-[4-phenyl-3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]acetate Chemical compound C1N(S(=O)(=O)CC(=O)OC)CCC(C=2C=C(C(C=3C=CC=CC=3)=CC=2)C(F)(F)F)=C1 CXMWZLRRELTEGW-UHFFFAOYSA-N 0.000 description 1
• ZFSLJVTWAJXSLK-UHFFFAOYSA-N methyl 4-[4-[4-(3-methoxyphenyl)-3-methylphenyl]piperidin-1-yl]sulfonyl-1-methylpiperidine-4-carboxylate Chemical compound C1CC(C=2C=C(C)C(=CC=2)C=2C=C(OC)C=CC=2)CCN1S(=O)(=O)C1(C(=O)OC)CCN(C)CC1 ZFSLJVTWAJXSLK-UHFFFAOYSA-N 0.000 description 1
• WOMOLSSVAJRPEA-UHFFFAOYSA-N methyl 4-[4-[4-(3-methoxyphenyl)-3-methylphenyl]piperidin-1-yl]sulfonyloxane-4-carboxylate Chemical compound C1CC(C=2C=C(C)C(=CC=2)C=2C=C(OC)C=CC=2)CCN1S(=O)(=O)C1(C(=O)OC)CCOCC1 WOMOLSSVAJRPEA-UHFFFAOYSA-N 0.000 description 1
• TXSWIMGHLUHJFE-UHFFFAOYSA-N methyl 4-[[4-(4-phenylphenyl)-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]oxane-4-carboxylate Chemical compound C1CC(C=2C=CC(=CC=2)C=2C=CC=CC=2)=CCN1S(=O)(=O)C1(C(=O)OC)CCOCC1 TXSWIMGHLUHJFE-UHFFFAOYSA-N 0.000 description 1
• QAMVFTZOSRZROU-UHFFFAOYSA-N methyl 4-[[4-[4-(3-ethoxyphenyl)-3-methylphenyl]-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]oxane-4-carboxylate Chemical compound CCOC1=CC=CC(C=2C(=CC(=CC=2)C=2CCN(CC=2)S(=O)(=O)C2(CCOCC2)C(=O)OC)C)=C1 QAMVFTZOSRZROU-UHFFFAOYSA-N 0.000 description 1
• FPFCCMXJTSSQHG-UHFFFAOYSA-N methyl 4-[[4-[4-(3-methoxyphenyl)-3-methylphenyl]-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]oxane-4-carboxylate Chemical compound C1CC(C=2C=C(C)C(=CC=2)C=2C=C(OC)C=CC=2)=CCN1S(=O)(=O)C1(C(=O)OC)CCOCC1 FPFCCMXJTSSQHG-UHFFFAOYSA-N 0.000 description 1
• WIQSGJXPICEZLP-UHFFFAOYSA-N methyl 4-[[4-[4-(4-ethoxyphenyl)-3-methylphenyl]-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]oxane-4-carboxylate Chemical compound C1=CC(OCC)=CC=C1C1=CC=C(C=2CCN(CC=2)S(=O)(=O)C2(CCOCC2)C(=O)OC)C=C1C WIQSGJXPICEZLP-UHFFFAOYSA-N 0.000 description 1
• VUQUOGPMUUJORT-UHFFFAOYSA-N methyl 4-methylbenzenesulfonate Chemical compound COS(=O)(=O)C1=CC=C(C)C=C1 VUQUOGPMUUJORT-UHFFFAOYSA-N 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• 239000003607 modifier Substances 0.000 description 1
• 150000002772 monosaccharides Chemical class 0.000 description 1
• 230000002107 myocardial effect Effects 0.000 description 1
• HQCBGSCOEUKQGA-UHFFFAOYSA-N n-[2-(2-fluorophenyl)ethyl]-3-(4-methyl-1,1,3-trioxo-1,2-thiazolidin-2-yl)benzamide Chemical compound O=C1C(C)CS(=O)(=O)N1C1=CC=CC(C(=O)NCCC=2C(=CC=CC=2)F)=C1 HQCBGSCOEUKQGA-UHFFFAOYSA-N 0.000 description 1
• XYXNUAHTTLZWPA-UHFFFAOYSA-N n-[2-(3,4-dimethoxyphenyl)ethyl]-2-[3-oxo-6-(trifluoromethyl)-4h-1,4-benzothiazin-2-yl]acetamide Chemical compound C1=C(OC)C(OC)=CC=C1CCNC(=O)CC1C(=O)NC2=CC(C(F)(F)F)=CC=C2S1 XYXNUAHTTLZWPA-UHFFFAOYSA-N 0.000 description 1
• IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
• RIVIDPPYRINTTH-UHFFFAOYSA-N n-ethylpropan-2-amine Chemical compound CCNC(C)C RIVIDPPYRINTTH-UHFFFAOYSA-N 0.000 description 1
• KKTSHMVWIWIUCV-UHFFFAOYSA-N n-hydroxy-1-[[4-(3-methyl-4-phenylphenyl)-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]cyclopentane-1-carboxamide Chemical compound CC1=CC(C=2CCN(CC=2)S(=O)(=O)C2(CCCC2)C(=O)NO)=CC=C1C1=CC=CC=C1 KKTSHMVWIWIUCV-UHFFFAOYSA-N 0.000 description 1
• DZKBXUUQLMNCGH-UHFFFAOYSA-N n-hydroxy-2-(4-phenylpiperidin-1-yl)sulfonylacetamide Chemical compound C1CN(S(=O)(=O)CC(=O)NO)CCC1C1=CC=CC=C1 DZKBXUUQLMNCGH-UHFFFAOYSA-N 0.000 description 1
• DORBNZHQHOCIEP-UHFFFAOYSA-N n-hydroxy-2-[(4-phenyl-3,6-dihydro-2h-pyridin-1-yl)sulfonyl]acetamide Chemical compound C1N(S(=O)(=O)CC(=O)NO)CCC(C=2C=CC=CC=2)=C1 DORBNZHQHOCIEP-UHFFFAOYSA-N 0.000 description 1
• RNRPMRLNLCZHAR-UHFFFAOYSA-N n-hydroxy-2-[3-(4-phenylphenoxy)azetidin-1-yl]sulfonylacetamide Chemical compound C1N(S(=O)(=O)CC(=O)NO)CC1OC1=CC=C(C=2C=CC=CC=2)C=C1 RNRPMRLNLCZHAR-UHFFFAOYSA-N 0.000 description 1
• WKVUGFBWMFZOMW-UHFFFAOYSA-N n-hydroxy-2-[4-(4-phenoxyphenyl)piperidin-1-yl]sulfonylacetamide Chemical compound C1CN(S(=O)(=O)CC(=O)NO)CCC1C(C=C1)=CC=C1OC1=CC=CC=C1 WKVUGFBWMFZOMW-UHFFFAOYSA-N 0.000 description 1
• OAQPUVCDKMAGGE-UHFFFAOYSA-N n-hydroxy-2-[4-(4-phenylphenyl)piperidin-1-yl]sulfonylacetamide Chemical compound C1CN(S(=O)(=O)CC(=O)NO)CCC1C1=CC=C(C=2C=CC=CC=2)C=C1 OAQPUVCDKMAGGE-UHFFFAOYSA-N 0.000 description 1
• MKBKQKMSVPLPFO-UHFFFAOYSA-N n-hydroxy-2-[4-[3-methoxy-4-(3-methoxyphenyl)phenyl]piperidin-1-yl]sulfonyl-2-methylpropanamide Chemical compound COC1=CC=CC(C=2C(=CC(=CC=2)C2CCN(CC2)S(=O)(=O)C(C)(C)C(=O)NO)OC)=C1 MKBKQKMSVPLPFO-UHFFFAOYSA-N 0.000 description 1
• STTXOLDYEVPGIB-UHFFFAOYSA-N n-hydroxy-2-[4-[4-(3-methoxyphenyl)-3-methylphenyl]piperidin-1-yl]sulfonyl-1,3-dihydroindene-2-carboxamide Chemical compound COC1=CC=CC(C=2C(=CC(=CC=2)C2CCN(CC2)S(=O)(=O)C2(CC3=CC=CC=C3C2)C(=O)NO)C)=C1 STTXOLDYEVPGIB-UHFFFAOYSA-N 0.000 description 1
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